scholarly journals Vasoactive Effects of Acute Ergot Exposure in Sheep

Toxins ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 291
Author(s):  
Rossalin Yonpiam ◽  
Jair Gobbet ◽  
Ashok Jadhav ◽  
Kaushik Desai ◽  
Barry Blakley ◽  
...  
Keyword(s):  
Single Dose ◽  
Chronic Exposure ◽  
Contractile Response ◽  
Ergot Alkaloids ◽  
Acute Exposure ◽  
Control Group ◽  
Vascular Effects ◽  
Adrenergic Antagonist ◽  
Vascular Sensitivity ◽  
Dose Dependent

Ergotism is a common and increasing problem in Saskatchewan’s livestock. Chronic exposure to low concentrations of ergot alkaloids is known to cause severe arterial vasoconstriction and gangrene through the activation of adrenergic and serotonergic receptors on vascular smooth muscles. The acute vascular effects of a single oral dose with high-level exposure to ergot alkaloids remain unknown and are examined in this study. This study had two main objectives; the first was to evaluate the role of α1-adrenergic receptors in mediating the acute vasocontractile response after single-dose exposure in sheep. The second was to examine whether terazosin (TE) could abolish the vascular contractile effects of ergot alkaloids. Twelve adult female sheep were randomly placed into control and exposure groups (n = 6/group). Ergot sclerotia were collected and finely ground. The concentrations of six ergot alkaloids (ergocornine, ergocristine, ergocryptine, ergometrine, ergosine, and ergotamine) were determined using HPLC/MS at Prairie Diagnostic Services Inc., (Saskatoon, SK, Canada). Each ewe within the treatment group received a single oral treatment of ground ergot sclerotia at a dose of 600 µg/kg BW (total ergot) while each ewe in the control group received water. Animals were euthanized 12 h after the treatment, and the pedal artery (dorsal metatarsal III artery) from the left hind limb from each animal was carefully dissected and mounted in an isolated tissue bath. The vascular contractile response to phenylephrine (PE) (α1-adrenergic agonist) was compared between the two groups before and after TE (α1-adrenergic antagonist) treatment. Acute exposure to ergot alkaloids resulted in a 38% increase in vascular sensitivity to PE compared to control (Ctl EC50 = 1.74 × 10−6 M; Exp EC50 = 1.079 × 10−6 M, p = 0.046). TE treatment resulted in a significant dose-dependent increase in EC50 in both exposure and control groups (p < 0.05 for all treatments). Surprisingly, TE effect was significantly more pronounced in the ergot exposed group compared to the control group at two of the three concentrations of TE (TE 30 nM, p = 0.36; TE 100 nM, p < 0.001; TE 300 nM, p < 0.001). Similar to chronic exposure, acute exposure to ergot alkaloids results in increased vascular sensitivity to PE. TE is a more potent dose-dependent antagonist for the PE contractile response in sheep exposed to ergot compared to the control group. This study may indicate that the dry gangrene seen in sheep, and likely other species, might be related to the activation of α1-adrenergic receptor. This effect may be reversed using TE, especially at early stages of the disease before cell death occurs. This study may also indicate that acute-single dose exposure scenario may be useful in the study of vascular effects of ergot alkaloids.

scholarly journals Genotoxic and Histopathological Effects of Chlorpyrifos on African Catfish, C. gariepinus and Ameliorative Potentials of Ackee Apple, blighia sapida Seed

2018 ◽  
Vol 6 (1) ◽  
pp. 1 ◽  
Author(s):  
Oluyinka Iyiolai ◽  
A. A. Adeagbo ◽  
W. S. Weliange ◽  
S. I. Abdulkareem ◽  
Anifowoshe T. Abass ◽  
...  
Keyword(s):  
Chronic Exposure ◽  
Clarias Gariepinus ◽  
Aquatic Organisms ◽  
Acute Exposure ◽  
Histopathological Analysis ◽  
African Catfish ◽  
Dependent Manner ◽  
Dose Dependent ◽  
Histopathological Effects ◽  
Positive Controls

Chlorpyrifos (CPF) is a very toxic pesticide commonly used for controlling agriculturally important pests. The present study investigates DNA damaging effects of CPF on Clarias gariepinus was assessed using genetic assays. Fish were exposed to varying concentrations of CPF (100ppm, 200ppm and 300ppm) at 96 hours (acute exposure). LC50 of the pesticide was found to be 120ppm and one-tenth of the LC50 (12ppm) was taken for the chronic exposure. Distilled water and colchicine were used as negative and positive controls respectively. After 28 days of chronic exposure, fish were fed with inclusion of B. sapida seed (powder) for 14 days. Liver and gills of the fish were removed following 96h exposure, days 7, 14 and 28 of the chronic exposure as well as after the period of amelioration (14 days) for CA assay and histopathological analysis. The results of CA assay showed statistically significant (p ˂ 0.05) increase in CA in a dose-dependent manner for all the exposed groups after acute exposure and time dependent after chronic exposure. Also, this study showed that CPF can potentially induce genotoxic and histopathological changes in fish and other aquatic organisms.

Effects of anesthetic agents on systemic critical O2 delivery

1991 ◽  
Vol 71 (1) ◽  
pp. 83-93 ◽  
Author(s):  
P. Van der Linden ◽  
E. Gilbart ◽  
E. Engelman ◽  
D. Schmartz ◽  
J. L. Vincent
Keyword(s):  
Low Dose ◽  
Control Group ◽  
High Dose ◽  
Vascular Effects ◽  
Anesthetic Agents ◽  
O2 Extraction ◽  
End Tidal ◽  
O2 Delivery ◽  
Dose Dependent ◽  
Intravenous Ketamine

The present study tested the hypothesis that anesthetic agents can alter tissue O2 extraction capabilities in a dog model of progressive hemorrhage. After administration of pentobarbital sodium (25 mg/kg iv) and endotracheal intubation, the dogs were paralyzed with pancuronium bromide, ventilated with room air, and splenectomized. A total of 60 dogs were randomized in 10 groups of 6 dogs each. The first group served as control (C). A second group (P) received a continuous infusion of pentobarbital (4 mg.kg-2.h-2), which was started immediately after the bolus dose. Three groups received enflurane (E), halothane (HL), or isoflurane (I) at the end-tidal concentration of 0.7 minimum alveolar concentration (MAC). The sixth group received halothane at the end-tidal concentration of 1 MAC (HH). Two groups received intravenous alfentanil at relatively low dose (AL) or high dose (AH). The last two groups received intravenous ketamine at either relatively low dose (KL) or high dose (KH). In each group, O2 delivery (Do2) was progressively reduced by hemorrhage. At each step, systemic Do2 and O2 consumption (VO2) were measured separately and the critical point was determined from a plot of Vo2 vs. Do2. The critical O2 extraction ratio (OER) in the control group was 65.0 +/- 7.8%. OER was lower in all anesthetized groups (P, 44.3 +/- 11.8%; E, 47.0 +/- 7.7%; HL, 45.7 +/- 11.2%; I, 44.3 +/- 7.1%; HH, 33.7 +/- 6.0%; AL, 56.5 +/- 9.6%; AH, 43.5 +/- 5.9%; KH, 57.7 +/- 7.1%), except in the KL group (78.3 +/- 10.0%). The effects of halothane and alfentanil on critical OER were dose dependent (P less than 0.05), whereas critical OER was significantly lower in the KH than in the KL group. Moreover, the effects of anesthetic agents on critical Do2 appeared related to their effects on systemic vascular resistance. Anesthetic agents therefore alter O2 extraction by their peripheral vascular effects. However, ketamine, with its unique sympathetic stimulant properties, had a lesser effect on OER than the other anesthetic agents. It could therefore be the anesthetic agent of choice in clinical situations when O2 availability is reduced.

scholarly journals Single-Dose Primaquine in a Preclinical Model of Glucose-6-Phosphate Dehydrogenase Deficiency: Implications for Use in Malaria Transmission-Blocking Programs

2016 ◽  
Vol 60 (10) ◽  
pp. 5906-5913 ◽  
Author(s):  
Kristina S. Wickham ◽  
Paul C. Baresel ◽  
Sean R. Marcsisin ◽  
Jason Sousa ◽  
Chau T. Vuong ◽  
...  
Keyword(s):  
Single Dose ◽  
Malaria Transmission ◽  
Hemolytic Anemia ◽  
G6pd Deficiency ◽  
Safety Data ◽  
Vehicle Control ◽  
Control Group ◽  
Vehicle Control Group ◽  
Glucose 6 Phosphate Dehydrogenase ◽  
Dose Dependent

ABSTRACTIndividuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency (G6PDd) are at risk for developing hemolytic anemia when given the antimalarial drug primaquine (PQ). The WHO Evidence Review Group released a report suggesting that mass administration of a single dose of PQ at 0.25 mg of base/kg of body weight (mpk) (mouse equivalent of 3.125 mpk) could potentially reduce malaria transmission based on its gametocytocidal activity and could be safely administered to G6PD-deficient individuals, but there are limited safety data available confirming the optimum single dose of PQ. A single-dose administration of PQ was therefore assessed in our huRBC-SCID mouse model used to predict hemolytic toxicity with respect to G6PD deficiency. In this model, nonobese diabetic (NOD)/SCID mice are engrafted with human red blood cells (huRBC) from donors with the African or Mediterranean variant of G6PDd (A-G6PDd or Med-G6PDd, respectively) and demonstrate dose-dependent sensitivity to PQ. In mice engrafted with A-G6PD-deficient huRBC, single-dose PQ at 3.125, 6.25, or 12.5 mpk had no significant loss of huRBC compared to the vehicle control group. In contrast, in mice engrafted with Med-G6PDd huRBC, a single dose of PQ at 3.125, 6.25, or 12.5 mpk resulted in a significant, dose-dependent loss of huRBC compared to the value for the vehicle control group. Our data suggest that administration of a single low dose of 0.25 mpk of PQ could induce hemolytic anemia in Med-G6PDd individuals but that use of single-dose PQ at 0.25 mpk as a gametocytocidal drug to block transmission would be safe in areas where A-G6PDd predominates.

Uses of single dose dependent and relative potency assays for the evaluation of inactivated fowl cholera vaccine

2019 ◽  
Vol 7 (2) ◽  
Author(s):  
Selim S Salama ◽  
Fatma M ◽  
Gadallah Fatma El Zahraa G ◽  
Abo Elkhir ◽  
Afaf A Khedrand ◽  
...  
Keyword(s):  
Single Dose ◽  
Relative Potency ◽  
Cholera Vaccine ◽  
Fowl Cholera ◽  
Dose Dependent

Biological and Phytochemical Screening of Tephrosia purpurea extract on Chemically Induced Hepatocellular Carcinoma with Reference to Biochemical Parameters

2019 ◽  
Vol 10 (02) ◽  
Author(s):  
Irfan Aziz ◽  
Birendra Shrivastava ◽  
Chandana Venkateswara Rao ◽  
Sadath Ali
Keyword(s):  
Free Radicals ◽  
Ethanolic Extract ◽  
Hepatoprotective Activity ◽  
Control Group ◽  
Marker Enzymes ◽  
Tephrosia Purpurea ◽  
Single Intraperitoneal Injection ◽  
Chemically Induced ◽  
Ccl4 Treatment ◽  
Dose Dependent

Tephrosia purpurea possesses hepatoprotective activity as evidenced by the significant and dose dependent restoring the activities of entire liver cancer marker enzymes, diminution in tumor incidence, decrease in lipid peroxidation (LPO) and increase in the level of antioxidant enzymes (GSH, CAT, SOD, GPx and GST) through scavenging of free radicals, or by enhancing the activity of antioxidant, which then detoxify free radicals. These factors protect cells from ROS damage in NDEA and CCl4-induced hepatocarcinogenesis. Histopathological observations of liver tissues too correlated with the biochemical observations. Thus, present investigation suggested that the Tephrosia purpurea would exert a chemoprotective effect by reversing the oxidant-antioxidant imbalance during hepatocarcinogenesis induced by NDEA and CCl4. Besides Tephrosia purpurea is very much effective in preventing NDEA-induced multistage hepatocarcinogenesis possibly through antioxidant and antigenotoxic nature, which was confirmed by various liver injury and biochemical tumour markers enzymes. The hepatoprotective activity of aTephrosia purpurea of 50 % ethanolic extract was studied using rats. The animals received a single intraperitoneal injection of N-nitrosodiethylamine 200mg/kg body wt followed by subcutaneous injection of CCl4 in a dose of 3 ml/kg body wt.Tephrosia purpureaextract dose dependently and significantly the increase in serum hepatic enzyme levels after NDEAand CCl4 treatment compared to the toxin control group. The results of this study confirmed the antioxidant and hepatoprotective activity of the Tephrosia purpurea extract against carbon tetrachlorideand N-nitrosodiethylamine induced hepatotoxicity in rats.

Liver, Kidney Function Tests and Oxidative Damage During and after Treatment of Salmonella typhimurium Infection in Experimental Local Rabbits

2018 ◽  
Vol 9 (4) ◽  
Author(s):  
Mustafa Salah Hasan ◽  
Ayman Barzan Abdulgafor ◽  
Maher Saber Owain ◽  
Mohammed Ali Hussein ◽  
Qusay Mohammed Aboud ◽  
...  
Keyword(s):  
Single Dose ◽  
Oxidative Damage ◽  
Salmonella Typhimurium ◽  
Infected Group ◽  
Post Treatment ◽  
Kidney Damage ◽  
Control Group ◽  
Post Inoculation ◽  
Group 5 ◽  
Group 2

This study aimed to evaluate the liver, kidney damage caused by S. typhimurium and to estimate the oxidative damage in association with this bacteria. A highly virulent isolates of S. typhimurium were obtained from the department of internal and preventive medicine/ College of Veterinary Medicine/ University of Baghdad. A twenty five local rabbits of both genders with age range (2-4 months) weeks old were used for this study, the rabbits were divided randomly into five groups each group contains 5 rabbits :- group 1: drenched orally with 5 ml of normal saline and consider as control group, group 2: were drenched orally with (5 ml) suspension which contain (5��109 CFU) of Salmonella typhimurium and regarded as infected group, group 3 were drenched orally with (5 ml) suspension which have (5��109 CFU) of Salmonella typhimurium then treated with a single dose of gentamicin alone at 0.05ml/kg (5mg/ml) orally after presence of signs (after 24hrs. post inoculation), group 4 were drenched (5 ml) suspension having (5��109 CFU) of Salmonella typhimurium then treated with a single dose of Ca-EDTA alone at 40mg/kg orally after presence of signs (after 24hrs. post inoculation) and group 5 were drenched (5 ml) suspension that contain (5��109 CFU) of Salmonella typhimurium then treated with a single dose of combined gentamicin at 0.05ml/kg (5mg/ml) orally after presence of signs (after 24hrs. post inoculation) and Ca-EDTA 40mg/kg after presence of signs (after 24hrs. post inoculation).The results of biochemical profile showed a significant increase (p less than 0.05) in ALT, creatinine and urea levels in infected group as compared with control group, while, the treated groups especially group 5 showed a significant improvement in ALT, Urea and creatinine levels which returned to relative normal levels as compared with infected group after 96hrs. post treatment. Also, the results of oxidative stress showed a significant increase in the levels of MDA in G2, G3, G4 and G5 after 48 hrs. post treatment, while the level of GSH showed a significant decrease in the level at 48hrs., both were returned to relative normal levels after 96hrs.post treatment especially in group 5.In conclusion, S. typhimurium can causing liver and kidney damage which is manifested by increase ALT, Urea and Creatinine. Also, MDA and GSH is increased due to salmonellosis.

TOKSISITAS AKUT INFUSA KULIT ARI KACANG TANAH (Arachis hypogea L.) PADA MENCIT BALB/ C

2018 ◽  
Vol 15 (2) ◽  
pp. 62
Author(s):  
Risha Fillah Fithria ◽  
Ririn Lispita Wulandari ◽  
Devi Nisa Hidayati ◽  
Lilis Rejeki
Keyword(s):  
Single Dose ◽  
Color Change ◽  
Negative Control ◽  
Control Group ◽  
Hair Color ◽  
Peanut Shell ◽  
Control Group Design ◽  
Safety Standards ◽  
Arachis Hypogea ◽  
Passive Behavior

ABSTRACTPeanut shell (PS) infusion has been shown to be antithrombocytopenia, but there has been no research on safety standards. This study aims to identify the symptoms of toxic effects, the potency of toxicity and histopathology of liver male Balb/C mice after a single dose of PS infusion. This research uses randomized matched posttest only control group design. Twenty five mice were divided into 5 orally dosage groups, ie, PS infusion with a dose of 0,026; 0.052; 0.104; 0.208 g/20gBW; and negative control of CMC Na 0.5%. The observation period is for 14 days. The results showed that single dose of PS infusion had a pseudo LD50 value ie > 0.208g/20gBW which was practically non toxic. Symptoms to watch out for the BW infusion were passive behavior, bradycnea, hair color change, hair loss, and weight loss at doses of 3 and 4. It is unclear whether liver damage ie inflammation, necrosis, and albuminous degeneration caused by PS infusion or other causes.keywords: acute toxicity, infusion, peanut shell

Protective effect of green tea extract against cadmium-induced testicular damage in rats in respect of oxidant/antioxidant equilibrium and androgen production

2020 ◽  
Vol 21 (1) ◽  
pp. 31-35
Author(s):  
Basma El-Desoky ◽  
Shaimaa El-Sayed ◽  
El-Said El-Said
Keyword(s):  
Gene Expression ◽  
Single Dose ◽  
Green Tea ◽  
Serum Testosterone ◽  
Green Tea Extract ◽  
Male Rats ◽  
Controlled Study ◽  
Control Group ◽  
Testicular Damage ◽  
Tea Extract

Objective: Investigating the effect of green tea extract (GTE) on the testicular damage induced by cadmium chloride CdCl2 in male rats. Design: Randomized controlled study. Animals: 40 male Wistar rats. Procedures: Rats were randomly divided into four groups: A) control group (each rat daily received pellet diet); B) GTE group each rat daily received pellet diet as well as 3 ml of 1.5 % w/v GTE, C) CdCl2 group each rat was I/P injected a single dose of 1 mg/kg CdCl2, then daily received pellet diet, and D) CdCl2+GTE group each rat was I/P injected a single dose of 1 mg/kg CdCl2 then daily received pellet diet as well as 3 ml of 1.5 % w/v GTE. After 30 days, blood samples were collected for hormonal assays (testosterone, FSH, and LH). In addition, both testes were collected; one of them was used for quantification of 17-beta hydroxysteroid dehydrogenase III (17β-HSDIII) gene expression using a real-time PCR. The other testis was used for determination of catalase and reduced glutathione; GSH, Nitric oxide (NO) and malondialdehyde (MDA) levels. Results: CdCl2 decreased serum testosterone levels and its synthesis pathway (17β-HSDIII testicular gene expression). While antioxidants catalase and GSH were reduced, oxidants MDA were enriched in the testes of CdCl2-poisoned rats. This CdCl2-promoted testicular dysfunction was corrected via the administration of GTE to male rats. Conclusion and clinical relevance: GTE could be used as a remedy for protecting against CdCl2-induced testicular damage in male rats.

scholarly journals Influence of group B streptococci on piglet pulmonary artery response to bradykinin

1999 ◽  
Vol 86 (1) ◽  
pp. 61-65 ◽  
Author(s):  
Richard M. Whitehurst ◽  
Rachel Laskey ◽  
Ronald N. Goldberg ◽  
Donald Herbert ◽  
Cornelius Van Breemen
Keyword(s):  
Pulmonary Artery ◽  
Contractile Response ◽  
Isometric Force ◽  
Control Group ◽  
Relaxed Controls ◽  
Vascular Response ◽  
Group B Streptococci ◽  
Resting Tension ◽  
Neonatal Group ◽  
Group B

To study whether a sepsis-induced increase in des-Arg9-bradykinin (des-Arg9-BK) and bradykinin (BK) B1-receptor activity participates in the observed increase in pulmonary vascular resistance in neonatal group B streptococcal sepsis (GBS), isometric force bioassays of pulmonary artery (PA) rings were studied, after 4-h exposure to either Krebs or GBS, by using the following protocols: 1) BK dose-response curve, 2) vascular response to BK with N G-nitro-l-arginine methyl ester (l-NAME), and 3) response to des-Arg9-BK (BK metabolite and B1 agonist). PA rings exposed to BK resulted in contraction in the GBS group and a decrease in resting tension in the Control group ( P = 0.034) at a concentration of 10−5 M. GBS-treated PA rings contracted more to des-Arg9-BK than did Controls ( P < 0.001). BK (10−6 M) relaxed preconstricted PA rings incubated in GBS less than BK relaxed Controls ( P < 0.001), and preincubation withl-NAME decreased relaxation in both. These results suggest that GBS decreased endothelium-dependent BK relaxation and increased contractile response to des-Arg9-BK. We speculate that this occurs secondary to upregulation of B1 receptors reflected by B1-agonist-mediated PA contraction.

scholarly journals Changes on proteomic and metabolomic profile in serum of mice induced by chronic exposure to tramadol

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Shukun Jiang ◽  
Guojie Liu ◽  
Huiya Yuan ◽  
Enyu Xu ◽  
Wei Xia ◽  
...  
Keyword(s):  
Chronic Exposure ◽  
Molecular Mechanisms ◽  
Fatty Acid Biosynthesis ◽  
Serum Proteins ◽  
Enzyme Inhibitor ◽  
Bile Secretion ◽  
Control Group ◽  
Protein Digestion ◽  
Metabolomic Profile ◽  
Apolipoprotein C

AbstractTramadol is an opioid used as an analgesic for treating moderate or severe pain. The long-term use of tramadol can induce several adverse effects. The toxicological mechanism of tramadol abuse is unclear. Limited literature available indicates the change of proteomic profile after chronic exposure to tramadol. In this study, we analyzed the proteomic and metabolomic profile by TMT-labeled quantitative proteomics and untargeted metabolomics between the tramadol and the control group. Proteomic analysis revealed 31 differential expressed serum proteins (9 increased and 22 decreased) in tramadol-treated mice (oral, 50 mg/kg, 5 weeks) as compared with the control ones. Bioinformatics analysis showed that the dysregulated proteins mainly included: enzyme inhibitor-associated proteins (i.e. apolipoprotein C-III (Apoc-III), alpha-1-antitrypsin 1–2 (Serpina 1b), apolipoprotein C-II (Apoc-II), plasma protease C1 inhibitor, inter-alpha-trypsin inhibitor heavy chain H3 (itih3)); mitochondria-related proteins (i.e. 14-3-3 protein zeta/delta (YWHAZ)); cytoskeleton proteins (i.e. tubulin alpha-4A chain (TUBA4A), vinculin (Vcl)). And we found that the differential expressed proteins mainly involved in the pathway of the protein digestion and absorption. Metabolomics analysis revealed that differential expressed metabolites mainly involved in protein ingestion and absorption, fatty acid biosynthesis, steroid hormone biosynthesis and bile secretion. Our overall findings revealed that chronic exposure to tramadol changed the proteomic and metabolomic profile of mice. Moreover, integrated proteomic and metabolomic revealed that the protein digestion and absorption is the common enrichment KEGG pathway. Thus, the combination of proteomics and metabolomics opens new avenues for the research of the molecular mechanisms of tramadol toxicity.

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